Role of TSP-1 and its receptor ITGB3 in the renal tubulointerstitial injury of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin ß3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expression of TSP-1 and ITGB3 were upregulated. We found that the expression of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The plasma level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. TSP-1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to bovine serum albumin and the adriamycin (ADR)-induced nephropathy model. THBS1 KO ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with bovine serum albumin, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.

Screening of potential drugs for the treatment of diabetic kidney disease using single-cell transcriptome sequencing and connectivity map data.

OBJECTIVE: To explore the feasibility of screening potential drugs for the treatment of diabetic kidney disease (DKD) using a single-cell transcriptome sequencing dataset and Connectivity Map (CMap) database screening. METHODS: A DKD single-nucleus transcriptome sequencing dataset was analyzed using Seurat 4.0 to obtain specific podocyte subclusters and differentially expressed genes (DEGs) related to DKD. These DEGs were subsequently subjected to a search against the CMap database to screen for drug candidates. Cell and animal experiments were conducted to evaluate the efficacy of the top 3 drug candidates. RESULTS: Initially, we analyzed the DKD single-nucleus transcriptome sequencing dataset to obtain intrinsic renal cells such as podocytes, endothelial cells, mesangial cells, proximal tubular cells, collecting duct cells and immune cells. Podocytes were further divided into four subclusters, among which the proportion of POD_1 podcytes was significantly greater in DKD kidneys than in control kidneys (34.0 % vs. 3.4 %). The CMap database was searched using the identified DEGs in the POD_1 subcluster, and the drugs, including tozasertib, paroxetine, and xylazine, were obtained. Cell-based experiments showed that tozasertib, paroxetine and xylazine had no significant podocyte toxicity in the concentration range of 0.01-50 µM. Tozasertib, paroxetine, and xylazine all reversed the advanced glycation end products (AGEs)-induced decrease in podocyte marker levels, but the effect of paroxetine was more prominent. Animal experiments showed that paroxetine decreased urine ALB/Cr levels in DKD model mice by approximately 51.5 % (115.7 mg/g vs. 238.8 mg/g, P < 0.05). Histopathological assessment revealed that paroxetine attenuated basement membrane thickening, restored the number of foot processes of podocytes, and reduced foot process fusion. In addition, paroxetine also attenuated renal tubular-interstitial fibrosis. Mechanistically, paroxetine inhibited the expression of GRK2 and NLRP3, decreased the phosphorylation level of p65, restored NRF2 expression, and relieved inflammation and oxidative stress. CONCLUSION: This strategy based on single-cell transcriptome sequencing and CMap data can facilitate the identification and aid the rapid development of clinical DKD drugs. Paroxetine, screened by this strategy, has excellent renoprotective effects.

Thermal image evaluation of crop diseases in the incubation period.

BACKGROUND: Early blight is one of the main diseases that causes serious pepper yield and quality reduction. The identification of the presymptomatic features during the incubation period is of great research significance, in that scientific prevention measures in the incubation period may effectively reduce the loss of peppers. RESULTS: The present study confirms the feasibility of the identification of presymptomatic features in pepper early blight by infrared thermography during the incubation period. The infrared thermal images of pepper blades were captured during the whole incubation period in our experiment. Evaluation parameters such as temperature uniformity (U) and the variation coefficient (C) were established by infrared thermal images for the blade temperature field. Evaluation parameters such as temperature uniformity U and variation coefficient C of pepper blades change during the time from being inoculated to significant morbidity. For cases of stabbing inoculation, there were no relatively obvious symptoms in visible light images until 96 h after inoculation, whereas some presymptomatic features appeared in infrared thermal images at 60 h after inoculation. Based on the uniformity changes (δU) and the variation coefficient changes (δC) in the temperature field distribution, the characteristic polynomial (CP)-GBDT model has been established by optimizing the gradient boosting decision tree (GBDT) model. Compared with the GBDT mode, the CP-GBDT model accuracy increased from 87.5% to 91.7% on the test set. CONCLUSION: Evaluation parameters such as temperature uniformity U and variation coefficient C can be used to effectively characterize the presymptomatic features of pepper early blight by infrared thermography during the incubation period. The results of the present study can provide a reference for the detection of crop diseases in the incubation period. © 2024 Society of Chemical Industry.

CD8 T Cell-Derived Exosomal miR-186-5p Elicits Renal Inflammation via Activating Tubular TLR7/8 Signal Axis.

T cells play an important role in the development of focal segmental glomerulosclerosis (FSGS). The mechanism underlying such T cell-based kidney disease, however, remains elusive. Here the authors report that activated CD8 T cells elicit renal inflammation and tissue injury via releasing miR-186-5p-enriched exosomes. Continuing the cohort study identifying the correlation of plasma level of miR-186-5p with proteinuria in FSGS patients, it is demonstrated that circulating miR-186-5p is mainly derived from activated CD8 T cell exosomes. Renal miR-186-5p, which is markedly increased in FSGS patients and mice with adriamycin-induced renal injury, is mainly delivered by CD8 T cell exosomes. Depleting miR-186-5p strongly attenuates adriamycin-induced mouse renal injury. Supporting the function of exosomal miR-186-5p as a key circulating pathogenic factor, intravenous injection of miR-186-5p or miR-186-5p-containing T cell exosomes results in mouse renal inflammation and tissue injury. Tracing the injected T cell exosomes shows their preferential distribution in mouse renal tubules, not glomerulus. Mechanistically, miR-186-5p directly activates renal tubular TLR7/8 signal and initiates tubular cell apoptosis. Mutating the TLR7-binding sequence on miR-186-5p or deleting mouse TLR7 largely abolishes renal tubular injuries induced by miR-186-5p or adriamycin. These findings reveal a causative role of exosomal miR-186-5p in T cell-mediated renal dysfunction.

Auxiliary-Cavity-Assisted Slow and Fast Light in a Photonic Molecule Spinning Optomechanical System.

We investigate the coherent optical propagation in a photonic molecule spinning optomechanical system consisting of two whispering gallery microcavities in which one of the optical cavities is a spinning optomechanical cavity and the other one is an ordinary auxiliary optical cavity. As the optomechanical cavity is spinning along the clockwise or counterclockwise direction, the cavity field can undergo different Sagnac effects, which accompanies the auxiliary optical cavity, together influencing the process of the evolution of optomechanically induced transparency and its related propagation properties, such as fast and slow light effects. The numerical results indicate that the enhanced slow and fast light and the conversion from fast to slow light (or slow to fast light) are determined by the spinning direction of the optomechanical cavity and the coupling of the two optical cavities. The study affords further insight into the photonic molecule spinning optomechanical systems and also indicates promising applications in quantum information processing.

Preparation, characteristics and cytotoxicity of green synthesized selenium nanoparticles using Paenibacillus motobuensis LY5201 isolated from the local specialty food of longevity area.

Selenium is an essential micronutrient element. For the extremely biotoxic of selenite, Selenium nanoparticles (SeNPs) is gaining increasing interest. In this work, a selenium-enriched strain with highly selenite-resistant (up to 173 mmol/L) was isolated from the local specialty food of longevity area and identified as Paenibacillus motobuensis (P. motobuensis) LY5201. Most of the SeNPs were accumulated extracellular. SeNPs were around spherical with a diameter of approximately 100 nm. The X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed that the purified SeNPs consisted of selenium and proteins. Our results suggested that P. motobuensis LY5201could be a suitable and robust biocatalyst for SeNPs synthesis. In addition, the cytotoxicity effect and the anti-invasive activity of SeNPs on the HepG2 showed an inhibitory effect on HepG2, indicating that SeNPs could be used as a potential anticancer drug.

[Seminal plasma exosomes and sperm DNA fragmentation index: A metabolomics analysis].

OBJECTIVE: To investigate the difference in the levels of metabolites in the seminal plasma exosomes (SPE) of men with a high sperm DNA fragmentation index (DFI) from those with a low DFI. METHODS: We performed a sperm exosomal metabolomics analysis of 5 healthy married men with DFI ≤15% (the control group) and another 5 with DFI ≥30% and matched in marital status, age and body mass index with the controls (the case group). Using high-performance liquid chromatography and mass spectrum, we examined the metabolites, observed their difference, and analyzed the metabolite enrichment pathway by Kyoto encyclopedia of genes and genomes (KEGG). According to the inclusion and exclusion criteria, we also selected 11 men in the control group and 20 men in the case group, and detected the differences in the seminal plasma amino acid and carnitine between the two groups using liquid measurement systems. RESULTS: After primary and secondary analyses and qualified screening, 23 metabolites related to sperm DNA integrity were obtained, including 9 organic acids, 2 amino acid intermediate metabolites, and 11 acylcarnitine, purine, niacin and other intermediate products. KEGG enrichment analysis showed that 23 metabolites were mainly involved in the sphingoid signaling pathway, niacin and niacinamide metabolic pathway, and arginine and proline metabolic pathway. Further verification revealed no difference in the level of seminal plasma amino acid between the two groups, and significantly lower levels of seminal plasma acylcarnitine, free carnitine, propionylcarnitine, 3-hydroxybutyrylcarnitine and malonylcarnitine, 3-hydroxyisovalerylcarnitine and succinylcarnitine, and isoamyl (enylcarnitine) in the case group than in the controls (P<0.05). CONCLUSION: There are significant differences in the levels of the metabolites organic acids, amino acids and acylcarnitine in the SPE of males with a high DFI from those with a low DFI. The level of seminal plasma acylcarnitine is significantly correlated with sperm DFI, which can be used as an indicator in quantitative and rapid assessment of the degree of sperm DNA damage.

Comparison of comfort and complications of Implantable Venous Access Port (IVAP) with ultrasound guided Internal Jugular Vein (IJV) and Axillary Vein/Subclavian Vein (AxV/SCV) puncture in breast cancer patients: a randomized controlled study.

BACKGROUND: Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. METHODS: Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. RESULTS: Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P < 0.001), day 2 (P < 0.001) and day 7(P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P < 0.001). More early complications occurred in AxV/SCV group than IJV group (11/124 vs 2/124, P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). CONCLUSIONS: Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.

Comparative Efficacy and Safety of TKIs Alone or in Combination With Antiangiogenic Agents in Advanced EGFR-Mutated NSCLC as the First-Line Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have suggested that patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) might benefit from the use of tyrosine kinase inhibitors (TKIs) in combination with antiangiogenic agents. This study aimed to comprehensively review the available evidence regarding the efficacy and safety of first-line TKI plus antiangiogenic agents versus TKIs alone in EGFR-mutated advanced NSCLC. MATERIALS AND METHODS: A literature search was performed using PubMed to identify studies published up to Feb. 2020. Abstracts from major international conferences reported over the last 5 years were searched. The primary outcome was progression-free survival (PFS), and the secondary outcomes included overall survival (OS), the objective response rate (ORR), and toxicity. RESULTS: In total, 7 relevant trials comprising 1612 patients were identified. TKIs plus antiangiogenic agents led to significant improvements in PFS regardless of the EGFR mutation subtype and presence of brain metastasis. In particular, in the subgroup with the L858R mutation, the hazard ratio (HR) of PFS was 0.58 (95% confidence interval [CI], 0.48-0.71, P < .001). The OS following combined treatment was similar to that following TKI monotherapy. The ORR was increased with the use of TKIs plus antiangiogenic agents (HR 1.10, 95% CI, 1.01-1.20, P = .029). In the safety analyses, TKIs plus antiangiogenic agents exhibited a significantly increased incidence of adverse events of grade 3 or higher. CONCLUSION: The use of TKIs plus antiangiogenic agents is associated with significantly improved PFS and ORR compared with TKIs alone in untreated EGFR-mutated NSCLC. The toxicities of combination therapy should be considered when making treatment choices.

Mental health comorbidities in adolescents and young adults with type 2 diabetes.

BACKGROUND: Screening for mental health comorbidities is recommended in adolescents and young adults (AYAs) with diabetes. There is a paucity of data on mental health comorbidities in AYAs with type 2 diabetes (T2D). OBJECTIVE: To assess rates of depression, suicidal ideation, and diabetes distress (DD) in AYAs with T2D overall and by sociodemographic and clinical factors. METHODS: AYAs with T2D ages 13-21 years seen in a pediatric diabetes clinic between March 2018 and June 2019 completed the Patient Health Questionnaire-9 (PHQ-9) for depression screening and the Problem Areas in Diabetes - teen version (PAID-T) survey to assess DD. Chi-square tests were used to assess whether rates of depression and DD were associated with participant characteristics. RESULTS: The sample consisted of 64 AYAs with T2D (58% female, mean age 15.8 ± 2.0 years, mean HbA1c 8.3% ± 2.6%, mean BMI z-score 2.2 ± 0.6, 59% on insulin). Overall, 31% of participants had high depression and/or DD. Twenty-two percent of participants reported high depressive symptoms and 9% endorsed suicidal ideation on the PHQ-9. There were no differences in rates of depression by sociodemographic factors. Twenty-three percent of participants reported high DD. Rates of DD were higher among those on insulin (p = 0.014) and on public health insurance (p = 0.014). CONCLUSIONS: Almost 1 in 3 AYAs with T2D endorsed depression and/or DD. Our findings support the importance of mental health screening in AYAs with T2D, as well as the need for strategies to address psychological comorbidities in this population.

Upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes.

Podocyte injury is a common hallmark in various glomerular diseases. The level of LRRC55 was increased in podocytes of patients with focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN), and membranous nephropathy (MN). Upregulated LRRC55 and increased intracellular Ca2+ led to BK channel activation and the loss of intracellular potassium, resulting in apoptosome formation and caspase-3 activation in angiotensin II (Ang II)-treated podocytes. Knockout of Lrrc55 or the BK channel prevented the BK current and ameliorated podocyte injury in Ang II-treated mice. Upstream, NFATc3 regulated the expression of LRRC55. Increased LRRC55 expression in podocytes was also evident in animal models of FSGS, DN, and MN. Treatment with losartan or LRRC55 siRNA suppressed LRRC55 expression, prevented BK channel activation, and attenuated podocyte injury in animal models of FSGS, DN, and MN. In conclusion, upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes in FSGS, DN, and MN. LRRC55 inhibition may represent a new therapeutic approach for podocyte injury.

Comparison of comfort and complications in breast cancer patients of implantable venous access port (IVAP) with ultrasound guided internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) puncture: a randomized controlled study protocol.

BACKGROUND: Internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer (BC) patients with chemotherapy. Previous studies focused on complications between these different approaches and ignored patient comfort. In this study, we aim to compare patient comfort between IJV and AxV/SCV approaches, as well as surgery duration and complications. METHODS: This is a single-center prospective randomized controlled clinical trial. A total of 200 patients diagnosed with invasive BC will be enrolled in this study. After signing written informed consent, patients schedule to undergo IVAP implantation will be randomized at a 1:1 ratio to receive central venous catheters (CVC) with either IJV or AxV/SCV approaches. Baseline as well as demographic data and procedure time of port implantation will be recorded. All patients will receive assessment of comfort with a comfort scale table at days 1, 2 and 7 after implantation surgery. Patients will be followed up and complications will be recorded until devices are removed at the end of the treatment period, or in case of complications. Patient comfort, procedure time of implantation and complications will be compared and analyzed between these two arms. DISCUSSION: To the best of our knowledge, this is the first study to compare patient comfort as primary outcome measure between IJV and AxV/SCV puncture. This study will further confirm the benefits of ultrasound guidance and may provide a better choice of IVAP implantation for BC patients. TRIAL REGISTRATION: This study has been registered at Chinese Clinical Trial Registry (ChiCTR, www. chictr.org.cn) and Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR2000034986).

[Highlights of PAPR Inhibitors in Small Cell Lung Cancer].

Small cell lung cancer (SCLC), characterized by early metastasis, relapse, relapse and resistance and poor prognosis, still faces difficulties in treatment. Recently, Immunotherapy is a novel treatment for SCLC, researchers are also eager to achieve a breakthrough in targeted treatment of SCLC. Genomic instability of SCLC and sensitivity to cytotoxic chemotherapy, therefore, poly ADP-ribose polymerase (PARP) inhibitors targeting DNA repair related pathways have become a hotspot in the research of SCLC targeted therapy. Studies on PARP inhibitors in SCLC have been conducted in combination with other therapeutic strategies, including the treatment of recurrent SCLC and first-line treatment,as well as maintenance treatment after induction. These studies also explored the predictive markers of PARP inhibitors in SCLC. Although the current results of PARP inhibitors in SCLC are limited, and the predictive markers are also inconsistent, we also see that PARP inhibitors could be a breakthroughfor precision medicine of SCLC.
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Assessment of Rates of Child Maltreatment in States With Medicaid Expansion vs States Without Medicaid Expansion.

Importance: Physical abuse and neglect affect a significant number of children in the United States. The 2014 Medicaid expansion, in which several states opted to expand their Medicaid programs, is associated with parental financial stability and access to mental health care. Objective: To determine whether Medicaid expansion is associated with changes in physical abuse and neglect rates. Design, Setting, and Participants: This ecological study used state-level National Child Abuse and Neglect Data Systems (NCANDS) data from January 1, 2010, through December 31, 2016, to compare the change in physical abuse and neglect rates in states that chose to expand Medicaid vs those that did not. All cases of physical abuse and neglect of children younger than 6 years during the study period that were referred to state-level Child Protective Services and screened in for further intervention after having met a maltreatment risk threshold were included. Cases with only documented sexual or emotional abuse were excluded. A difference-in-difference analysis was conducted from April 12, 2018, through March 26, 2019. Exposures: State-level Medicaid expansion status. Main Outcomes and Measures: Incidence rate of screened-in referrals for physical abuse or neglect per 100 000 children younger than 6 years per year by state. Results: Data were analyzed for 31 states and the District of Columbia that expanded Medicaid and 19 states that did not during the study period, with baseline neglect counts of 646 463 and 388 265, respectively. After Medicaid expansion, 422 fewer cases of neglect per 100 000 children younger than 6 years (95% CI, -753 to -91) were reported each year after adjusting for confounders for comparison of postexpansion and preexpansion rates in states that expanded Medicaid contrasting with the change during that time in nonexpansion states. From 2013 to 2016, Medicaid coverage for adults with dependent children increased a median 1.9% (interquartile range, 0.4% to 4.3%) in the states that did not expand Medicaid and 4.2% (interquartile range, 0.9% to 6.0%) in the states that did. No associations were found between Medicaid coverage or Medicaid eligibility criteria and physical abuse or neglect rates. Conclusions and Relevance: Medicaid expansion was associated with a reduction in the reported child neglect rate, but not the physical abuse rate. These findings suggest that expanding Medicaid may help prevent child neglect.

C3a and suPAR drive versican V1 expression in tubular cells of focal segmental glomerulosclerosis.

Chronic tubulointerstitial injury impacts the prognosis of focal segmental glomerulosclerosis (FSGS). We found that the level of versican V1 was increased in tubular cells of FSGS patients. Tubular cell-derived versican V1 induced proliferation and collagen synthesis by activating the CD44/Smad3 pathway in fibroblasts. Both urine C3a and suPAR were increased and bound to the tubular cells in FSGS patients. C3a promoted the transcription of versican by activating the AKT/ß-catenin pathway. C3aR knockout decreased the expression of versican in Adriamycin-treated (ADR-treated) mice. On the other hand, suPAR bound to integrin ß6 and activated Rac1, which bound to SRp40 at the 5' end of exon 7 in versican pre-mRNA. This binding inhibited the 3'-end splicing of intron 6 and the base-pair interactions between intron 6 and intron 8, leading to the formation of versican V1. Cotreatment with ADR and suPAR specifically increased the level of versican V1 in tubulointerstitial tissues and caused more obvious interstitial fibrosis in mice than treatment with only ADR. Altogether, our results show that C3a and suPAR drive versican V1 expression in tubular cells by promoting transcription and splicing, respectively, and the increases in tubular cell-derived versican V1 induce interstitial fibrosis by activating fibroblasts in FSGS.

Upregulated long noncoding RNA LOC105375913 induces tubulointerstitial fibrosis in focal segmental glomerulosclerosis.

Tubulointerstitial fibrosis impacts renal prognosis of focal segmental glomerulosclerosis (FSGS). Based on transcriptomic analysis, we found that the level of LOC105375913 was increased in tubular cells of FSGS patients. C3a induced the expression of LOC105375913, which promoted the expression of fibronectin and collagen I in tubular cells. Silence of snail reversed the level of fibronectin and collagen I in cells overexpressing LOC105375913. MiR-27b was predicted and confirmed to regulate the expression of snail in tubular cells, and LOC105375913 contained the response element of miR-27b. The competitive binding between LOC105375913 and miR-27b increased the level of snail and promoted fibrogenesis in tubular cells. Upstream, p38 and XBP-1s regulated the expression of LOC105375913. Inhibition of p38 or silence of XBP-1s decreased the level of LOC105375913, and suppressed the expression of snail, fibronectin and collagen I in tubular cells treated with C3a. Overexpression of LOC105375913 decreased the level of miR-27b, increased the level of snail and caused tubulointerstitial fibrosis in mice. In conclusion, the activation of C3a/p38/XBP-1s pathway induces the expression of LOC105375913 in tubular cells, and LOC105375913 increases the level of snail and induces tubulointerstitial fibrosis through competitive binding of miR-27b in tubular cells of FSGS patients.

A cross-sectional survey based on blood VOCs, hematological parameters and urine indicators in a population in Jilin, Northeast China.

The objective of this study was to examine whether long-term exposure to low-dose volatile organic compounds (VOCs) will have an effect on the health of non-occupational population. A total of 499 non-occupational participants aged more than 18 that live around Jilin Petrochemical Industrial Zone were chosen by stratified cluster random sampling. Their blood VOCs' levels, hematological parameters and urine indicators together with detailed questionnaire data were used to find possible relationships using binary logistic regression analysis. The detection rate of benzene in the blood was high in the non-occupational population around the industrial area, and it even reached 82.3% in males but no significant difference was recorded between male and female population. In addition, trichloroethane (male: 33.2% V female: 21.7%; p = 0.002), carbon tetrachloride (males: 20.3% V females: 7.5%; p < 0.001) and trichlorethylene (male: 34.9% V female: 24.7%; p = 0.004) all showed significant differences in gender, and without exception, the prevalence of males was higher in these three VOCs than of females. The changes in red blood cell (RBC), hematocrit (HCT) and basophils are correlated with carbon tetrachloride, trichloroethylene and chloroform, respectively. And RBC, HCT and basophils are statistically significant in male compared with female of the study population. The increase in trichlorethylene was associated with an increase of 1.723% (95% CI 1.058-2.806) in HCT. The increase in carbon tetrachloride showed a more significant correlation with an increase of 2.638% in RBC count (95% CI 1.169-5.953). And trichloromethane led to a 1.922% (95% CI 1.051-3.513) increase in basophils. The changes in urinary WBC, urine ketone (KET) and urinary bilirubin (BIL) showed significant correlation with benzene, carbon tetrachloride and dibromochloromethane, respectively. The correlation in females is more significant than in males. The increase of benzene in the female population increased urinary leukocyte count by 2.902% (95% CI 1.275-6.601). The effect of carbon tetrachloride on KET was particularly pronounced, resulting in an increase of 7.000% (95% CI 1.608-30.465). Simultaneously, an increase in dibromochloromethane caused an increase of 4.256% (95% CI 1.373-13.192) in BIL. The changes in RBC, HCT and basophils can only serve as an auxiliary indicator for disease diagnosis, so they have no significant clinical significance. However, the alteration of urinary WBC, KET and BIL has great clinical significances, and it is suggested that the monitoring of the above indicators from low-dose long-term exposure be strengthen in this area.

The long noncoding RNA LOC105374325 causes podocyte injury in individuals with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a common kidney disease that results in nephrotic syndrome. FSGS arises from dysfunction and apoptosis of podocytes in the glomerulus of the kidney, leading to podocytopathy. The molecular mechanisms underlying podocyte apoptosis remain incompletely understood. Using an array of gene expression profiling, PCR, and in situ hybridization assay, we found here that the levels of the long noncoding RNA LOC105374325 were elevated in the renal podocytes of individuals with FSGS. We also observed that the microRNAs miR-34c and miR-196a/b down-regulated the expression of the apoptosis regulators BCL2-associated X, apoptosis regulator (Bax), and BCL2 antagonist/killer 1 (Bak) in podocytes. Competitive binding between LOC105374325 and miR-34c or miR-196a/b increased Bax and Bak levels and caused podocyte apoptosis. Of note, the mitogen-activated protein kinase P38 and the transcription factor CCAAT enhancer-binding protein ß (C/EBPß) up-regulated LOC105374325 expression. P38 inhibition or C/EBPß silencing decreased LOC105374325 levels and inhibited apoptosis in adriamycin-treated podocytes. LOC105374325 overexpression decreased miR-34c and miR-196a/b levels, increased Bax and Bak levels, and induced proteinuria and focal segmental lesions in mice. In conclusion, activation of the P38/C/EBPß pathway stimulates the expression of LOC105374325, which, in turn, increases Bax and Bak levels and causes apoptosis by competitively binding to miR-34c and miR-196a/b in the podocytes of individuals with FSGS.

Development of a low-cost paper-based ELISA method for rapid Escherichia coli O157:H7 detection.

Escherichia coli O157: H7 (E. coli O157: H7) has become one of the most dangerous foodborne pathogenic bacteria around the world. Currently, because of the tedious, high-cost and stringent laboratory conditions required, the conventional E. coli O157: H7 detection methods, such as culture-based methods and polymerase chain reaction (PCR), have much limitation. Thus, we developed a novel paper-based enzyme-linked immunosorbent assay (p-ELISA) with shorter operation duration, lower cost, relatively higher sensitivity and wider application. This method required less than 3 h and 5 µL of sample to complete the detection. The limit of detection (LOD) for E. coli O157: H7 reached 1 × 104 CFU/mL with high specificity. To be more suitable for on-site testing, the readout could be rapidly obtained without any expensive instruments. In this study, we chose E. coli O157:H7 as the representative, and our method could provide a platform for determination of other pathogenic bacteria.